Histamine is a hydrophilic vasoactive amine, or an important messenger molecule released from activated mast cells, white blood cells called basophils, enterochromaffin-like cells, and neurons. Histamine plays a pathophysiological regulatory role in cellular events through binding to four types of histamine receptors (i.e. H1R, H2R, H3R and H4R), they being G-protein-coupled receptors with histamine as their endogenous ligand.
The various biological effects of histamine mediated through the activation of specific histamine H1, H2, H3 and H4 receptors differ in their tissue expression patterns and functions. All four types known histamine receptors (i.e. H1R, H2R, H3R, and H4R) have been used or proposed as therapeutic targets for a wide variety of diseases. Histamine H1 receptor causes systemic vasodilatation, smooth muscle contraction, separation of endothelial cells, potentiation of pain, and pruritus etc. Histamine H2 receptor is primarily involved in vasodilation and also stimulates gastric acid secretion. Histamine H3 receptor decreases neurotransmitters (e.g. histamine, etc.) release from the neurons. Histamine H4 receptor has been shown to be involved in chemotaxis and inflammatory mediators released by eosinophils, mast cells, monocytes, dendritic cells, and T cells.
Histamine receptor antagonists to block action of histamine have found use in therapy for the various diseases, such as allergic inflammatory conditions, tissue and organ fibrosis, different diseases associated with abnormal neurotransmitter levels, immune system disorders, and the conditions or disorders involved in abnormal cell proliferation including both benign and malignant tumor cells, etc.
However, conventional medicines may often cause uncertain side effects. For example, Loratadine (or Claritin, Claritin RediTabs, etc.), one of histamine H1 receptor antagonists may commonly cause headache, drowsiness, fatigue and dry mouth. In addition, major side effects of Famotidine (i.e. Pepcid, a histamine H2 receptor antagonist) include constipation, diarrhea, fatigue, headache, insomnia, muscle pain, nausea, and vomiting.
Additionally, inhaled corticosteroids are first-line agents for conventional treatment in severe acute asthma attacks mediated by histamine receptors; and the administration of corticosteroids and pharmaceutical compositions comprising corticosteroids can promote wound healing and reduce scar formation, as described in international patent application publication WO/2011/006100 Method of Wound Healing and Scar Modulation. But, long-term use of corticosteroids can have many side effects including thinning of the skin and easy bruising, a redistribution of fat, increased appetite, weight gain, blood glucose problems, insomnia, and emotional changes, etc.
Furthermore, it is known that nasal congestion or stuffy nose, one of symptoms of allergic rhinitis, is the blockage of the nasal passages usually due to membranes lining of the nose becoming swollen resulting from inflamed blood vessels. Decongestants can provide significant symptom relief of nasal congestion. Clinically, topical decongestants are generally used to apply directly to the nasal cavity to relieve nasal congestion in order to reduce the side effects associated with systemically-acting decongestants. For example, phenylephrine, the most common over-the-counter (OTC) decongestant in the United States, used as a decongestant and sold as an oral medicine, nasal spray, or eye drops, but one of side effects is high blood pressure caused by vasoconstriction.
However, topical decongestants should only be used by patients for a maximum of three days in a row because rebound congestion may occur in the form of rhinitis medicamentosa that is a condition of rebound nasal congestion brought on by extended use of topical decongestants, such as oxymetazoline, a more common nasal spray. Decongestants are normally paired with antihistamines to lessen this effect, but the combination of both classes of drugs does not necessarily cancel the side effects of each other. The common side effects of decongestants include sleeplessness, anxiety, dizziness, excitability, and nervousness besides hypertension.
Accordingly, patients may be seeking out alternative treatments to avoid the adverse effects of conventional treatments that may be invasive and expensive, and there is a need in the art for a safe and effective alternative method by which to treat and/or prevent the conditions or disorders mediated by histamine, particularly, natural products for promotion of health as well as treatment of disease.